HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 8, 5168-5177, February 22, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/8/5168    most recent M709043200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Niles, B. J. Articles by Keen, C. L. Search for Related Content PubMed PubMed Citation Articles by Niles, B. J. Articles by Keen, C. L. Social Bookmarking                      What's this?

Zinc Deficiency-induced Iron Accumulation, a Consequence of Alterations in Iron Regulatory Protein-binding Activity, Iron Transporters, and Iron Storage Proteins^*

Brad J. Niles, Michael S. Clegg, Lynn A. Hanna, Susan S. Chou, Tony Y. Momma, Heeok Hong, and Carl L. Keen^¶1

From the Departments of Nutrition and ^¶Internal Medicine, University of California, Davis, California 95616-8669 and the Department of Food Service Management and Nutrition, Sangmyung University, Seoul 110-743, Korea

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 µM zinc), zinc-supplemented (S, 50 µM zinc), or control (C, 4 µM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Received for publication, November 5, 2007 , and in revised form, December 4, 2007.

^* This work was supported by National Institutes of Health Grants HD01743 and DK07355 (to B. J. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Nutrition, University of California, One Shields Ave., Davis, CA 95616-8669. Tel.: 530-752-6331; Fax: 530-752-8966; E-mail: clkeen{at}ucdavis.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?